详细内容（前10条）

1. ⭐ GSE293728 IFN-γ-STAT1轴驱动肿瘤相关巨噬细胞中MHC-II抗原呈递增强

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、antigen、MHC
• 📝 描述：Contributors : Naixue Yang ; Hao Yuan ; Xun LanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWhile the IFN-γ-STAT1 signaling pathway is well-characterized in promoting MHC class II (MHC-II)-dependent antigen presentation within pro-inflammatory macrophages during acute infections, its functional dynamics in tumor-associated macrophages (TAMs) remain poorly understood. Here, we systematically investigated the immunomodulatory role of IFN-γ-STAT1 axis in TAMs through integrative bioinformatics and experimental validation. Transcriptomic analysis of tumor-infiltrating myeloid cells across multiple cancer cohorts revealed a strong correlation between STAT1 activation and MHC-II pathway enrichment, particularly in IFN-γ-high TAM subsets. To mechanistically dissect this relationship, we employed bone marrow-derived macrophages (BMDMs) polarized under tumor-conditioned media and subjected them to IFN-γ stimulation. Single-cell RNA sequencing demonstrated that IFN-γ triggered STAT1 nuclear translocation, upregulating MHC-II genes. Our findings establish IFN-γ-STAT1 as a master regulator of TAM immunogenicity, proposing targeted STAT1 activation as a strategy to overcome myeloid-driven immunosuppression in cancer.
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2. GSE282101 VISTA 通过调节肿瘤相关巨噬细胞极性驱动胰腺肿瘤进展

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、macrophage
• 📝 描述：Contributor : Suk-Kyung ShinSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies due to its highly immunosuppressive tumor microenvironment (TME), which limits effective therapeutic interventions. Here, we demonstrate that V-domain immunoglobulin suppressor of T cell activation (VISTA) plays a crucial role in orchestrating macrophage polarity within the PDAC TME. Using murine PDAC models, we show that VISTA deficiency markedly impairs tumor growth, leading to reduced tumor volumes and prolonged survival. Mechanistically, VISTA loss reprograms tumor-associated macrophages (TAMs) from an immunosuppressive, secreted phosphoprotein 1(SPP1) expressing phenotype to a pro-inflammatory, C-X-C motif chemokine ligand 9 (CXCL9) expressing subtype. This switch enhances the recruitment of C-X-C motif chemokine receptor 3 (CXCR3) positive CD8+ T cells, reducing their exhaustion and sustaining their cytotoxic activity. Additionally, VISTA-deficient TAMs exhibit increased antigen cross-presentation, further amplifying CD8+ T cell response against tumors. These findings are corroborated by human single cell RNA-seq datasets, which suggest a conserved mechanism of VISTA-mediated immune modulation in PDAC TME. By elucidating the upstream role of VISTA in driving Cxcl9:Spp1 macrophage polarity and T cell dynamics, this study highlights VISTA inhibition as a promising therapeutic strategy to reshape the TME, augment CD8+ T cell function, and enhance anti-tumor immunity in PDAC.
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3. GSE313915 FOXA1 缺失通过释放基底/鳞状细胞去分化和免疫抑制微环境诱发侵袭性前列腺癌 [ChIP-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ChIP-seq
• 📝 描述：Contributors : Lourdes Brea ; Qi Chu ; Jonathan C Zhao ; Jindan YuSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusFOXA1 is an epithelial transcription factor that is often found dysregulated in prostate cancer. Previous studies have reported both tumor-promoting and -inhibitory functions of FOXA1. However, a comprehensive analysis of FOXA1 in a physiological, immune-competent setting is still lacking. We here report a novel genetically engineered mouse model with Foxa1 KO in the Pten-null prostate epithelium for the study of FOXA1 loss within an immune-competent prostate tumor context. Here, we report Foxa1 loss induces prostate cancer lineage switch from a luminal-like to a more aggressive basal/squamous-like phenotype, which is accompanied by inflammatory and immunosuppressive cytokine signaling. Mechanistically, in addition to inducing luminal genes, we found FOXA1 directly inhibits several basal/squamous, inflammatory, and cytokine genes, such that its loss unleashes their expression. Moreover, Foxa1 loss induces a striking remodeling of the prostate tumor immune microenvironment, leading to increased immunosuppressive myeloid accumulation and dysfunctional and spatially confined T cells. Altogether, we report critical roles for FOXA1 loss in inducing basal/squamous de-differentiation and an immunosuppressive microenvironment.
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4. GSE282725 FOXA1 缺失通过释放基底/鳞状细胞去分化和免疫抑制微环境诱发侵袭性前列腺癌 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、scRNA
• 📝 描述：Contributors : Lourdes Brea ; Viriya Keo ; Jonathan C Zhao ; Jindan YuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusFOXA1 is an epithelial transcription factor that is often found dysregulated in prostate cancer. Previous studies have reported both tumor-promoting and -inhibitory functions of FOXA1. However, a comprehensive analysis of FOXA1 in a physiological, immune-competent setting is still lacking. We here report a novel genetically engineered mouse model with Foxa1 KO in the Pten-null prostate epithelium for the study of FOXA1 loss within an immune-competent prostate tumor context. Here, we report Foxa1 loss induces prostate cancer lineage switch from a luminal-like to a more aggressive basal/squamous-like phenotype, which is accompanied by inflammatory and immunosuppressive cytokine signaling. Mechanistically, in addition to inducing luminal genes, we found FOXA1 directly inhibits several basal/squamous, inflammatory, and cytokine genes, such that its loss unleashes their expression. Moreover, Foxa1 loss induces a striking remodeling of the prostate tumor immune microenvironment, leading to increased immunosuppressive myeloid accumulation and dysfunctional and spatially confined T cells. Altogether, we report critical roles for FOXA1 loss in inducing basal/squamous de-differentiation and an immunosuppressive microenvironment.
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5. GSE282724 FOXA1 缺失通过释放基底/鳞状细胞去分化和免疫抑制微环境诱发侵袭性前列腺癌 [Visium]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、Visium
• 📝 描述：Contributors : Lourdes Brea ; Viriya Keo ; Jonathan C Zhao ; Jindan YuSeries Type : OtherOrganism : Mus musculusFOXA1 is an epithelial transcription factor that is often found dysregulated in prostate cancer. Previous studies have reported both tumor-promoting and -inhibitory functions of FOXA1. However, a comprehensive analysis of FOXA1 in a physiological, immune-competent setting is still lacking. We here report a novel genetically engineered mouse model with Foxa1 KO in the Pten-null prostate epithelium for the study of FOXA1 loss within an immune-competent prostate tumor context. Here, we report Foxa1 loss induces prostate cancer lineage switch from a luminal-like to a more aggressive basal/squamous-like phenotype, which is accompanied by inflammatory and immunosuppressive cytokine signaling. Mechanistically, in addition to inducing luminal genes, we found FOXA1 directly inhibits several basal/squamous, inflammatory, and cytokine genes, such that its loss unleashes their expression. Moreover, Foxa1 loss induces a striking remodeling of the prostate tumor immune microenvironment, leading to increased immunosuppressive myeloid accumulation and dysfunctional and spatially confined T cells. Altogether, we report critical roles for FOXA1 loss in inducing basal/squamous de-differentiation and an immunosuppressive microenvironment.
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6. GSE256187 超级增强子重组控制奥沙利铂耐药 FBXW7 突变结直肠癌的再敏感性 [ChIP-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ChIP-seq
• 📝 描述：Contributors : Nicolò Gualandi ; Vanessa Tolotto ; Ylenia Cortolezzis ; Eros Di GiorgioSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensEpigenetic plasticity and large-scale chromatin remodeling characterize tumor evolution and the emergence of subclones resistant to conventional therapies. Catalytically inactive class IIa HDACs (HDAC4, HDAC5, HDAC7, HDAC9) act as acetyl-lysine readers that form the scaffold for the targeted recruitment of chromatin remodeling complexes, making them very attractive therapeutic targets in the field of oncology.In this study, we found that HDAC4 is proteasomal degraded in cancer cells impaired in DNA repair by homologous recombination. Genetic screening identified FBXW7 as the E3 ligase responsible for this degradation. FBXW7 loss-of-function mutations are frequently found in patients with colorectal cancer (CRC), and FBXW7 mutation status is associated with the development of resistance to oxaliplatin. Deletion of HDAC4 or its forced degradation with a PROTAC-based compound restored oxaliplatin sensitivity in FBXW7-mutated CRC cells, patient-derived organoids (PDOs) and xenografts, with no effect on DNA damage response activation or DNA platination.Mechanistically, forced removal of HDAC4 in FBXW7-mutant CRC cells and PDOs treated with oxaliplatin resulted in a deep rearrangement of the super-enhancer landscape, with a dramatic loss of super-enhancers found in oxalipaltin-resistant samples and restoration of certain super-enhancers found in oxaliplatin-sensitive cells. The disassembly of HDAC4 complexes achieved with Tasquinimod partially recapitulated the effects obtained with the PROTAC-based HDAC4 compound, demonstrating the importance of the epigenetic function of HDAC4 in supporting drug resistance.This study supports HDAC4 as a key mediator of oxaliplatin resistance in FBXW7-mutated CRC and highlights the remodeling of a well-defined repertoire of super-enhancers as part of the process of successful re-sensitization.
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7. GSE213095 cDC1s 和 CD8+ T 细胞之间的正反馈是 HLA-B27+ 关节炎炎症的典型特征

• ✍️ 作者：未知作者
• 🏷️ 关键词：inflammation、HLA
• 📝 描述：Contributors : Fenli Shao ; Zhigui WuSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensEnthesitis-related arthritis (ERA) is a subtype of juvenile idiopathic arthritis (JIA) with enthesitis and sacroiliitis, which differ from other types of JIA in symptoms, pathogenesis, and outcome. Although the association of human leukocyte antigen-B27 (HLA-B27) with ERA has been confirmed for decades, the pathogenesis of ERA is poorly understood. Here, we performed single-cell RNA-seq of 1,73,134 mononuclear cells extricated from patients with oligoarthritis (OligoA) or ERA and integrated 58,725 PBMCs of healthy people to profile the immune characteristic that discriminates ERA from OligoA. We found that conventional type 1 dendritic cells (cDC1s) were enriched in the joints of patients with ERA and exhibited a high level of MHC class I antigen presentation. Central memory CD8+ T cells critically contributed to the elevation of XCL1, recruiting XCR1+ cDC1 in joints of ERA. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) analyses confirmed an increased proportion and interaction of cDC1s and CD8+ T cells. In addition, macrophages occupied the causal position in the pathogenesis of OligoA, along with high expression of MHC class II molecules on macrophages and cDC2s in the joints. This study suggests that the positive feedback between cDC1s and CD8+ T cells is a key mediator of HLA-B27-positive arthritis pathogenesis.
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8. GSE318177 DNA methylation in episodic migraine and medication overuse headache.

• ✍️ 作者：未知作者
• 🏷️ 关键词：methylation
• 📝 描述：Contributors : Katarzyna M Kwiatkowska ; Paolo Garagnani ; Sabina CevoliSeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensThese data were generated within the Epimode project - a pilot, longitudinal, prospective, observational study designed to investigate DNA methylation in headache disorders. 20 episodic migraineurs (EM), 25 medication overuse headache patients (MOH) and 13 healthy controls (HC) were enrolled in the study. EM and HC samples were collected at baseline (T0) and ath the follow-up visit 6 months later (T1). MOH samples were collected at baseline (T0), at treatment time point (T1) and at the follow-up visits after 2 (T2) and 6 (T3) months from the therapeutic intervention. Genome-wide methylation data for overall 142 DNA (WB) samples were generated using Illumina Infinium Methylation EPIC v1.0 BeadChip. Generated dataset allowed us to analyse differential signatures, methylation clocks and stochastic epigenetic mutations related to EM, MOH and response to the treatment.
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9. GSE282726 FOXA1缺失通过释放基底/鳞状细胞去分化和免疫抑制微环境诱发侵袭性前列腺癌

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer
• 📝 描述：Series Type : Other ; Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusThis SuperSeries is composed of the SubSeries listed below.
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10. GSE282721 FOXA1 缺失通过释放基底/鳞状细胞去分化和免疫抑制微环境诱发侵袭性前列腺癌 [CosMx]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer
• 📝 描述：Contributors : Lourdes Brea ; Viriya Keo ; Jonathan C Zhao ; Jindan YuSeries Type : OtherOrganism : Homo sapiensForkhead box A1 (FOXA1) is a lineage-specifying transcription factor that is often de-regulated prostate cancer (PCa), with previous studies reporting both tumor-promoting and -inhibitory functions. Little is known about FOXA1 function in a physiological setting of PCa progression. Here we report that Foxa1 knockout in the Pten-null prostate epithelium in vivo leads to an aggressive sub-type of PCa marked by basal/squamous de-differentiation, tissue disorganization, and poor survival. Single-cell RNA-seq revealed a major increase of basal/squamous gene expression in the epithelium, which was accompanied by inflammatory and immunosuppressive cytokine signaling. Mechanistically, in addition to its well-known role in inducing luminal genes, FOXA1 directly inhibits many basal/squamous and inflammatory genes, which are unleashed upon Foxa1 knockout. Significantly, there is a striking remodeling of the tumor immune microenvironment in Foxa1-depleted PCa, with increased tumor infiltration by immunosuppressive myeloid populations and dysfunctional and spatially confined T cells. These important findings were further confirmed in human PCa samples via single-cell and spatial transcriptomic analyses. Altogether, we report critical roles for FOXA1 loss in inducing basal/squamous de-differentiation and an immunosuppressive microenvironment.
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1. 超级马拉松可能会损害红细胞并加速衰老。

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging
• 📝 描述：Running extreme distances may strain more than just muscles and joints. New research suggests ultramarathons can alter red blood cells in ways that make them less flexible and more prone to breakdown, potentially interfering with how they deliver oxygen throughout the body. Scientists found signs of both mechanical stress from intense blood flow and molecular damage linked to inflammation and oxidative stress.
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• GSE307658 流感感染期间 MHCII-KO 和 WT B 细胞的单细胞 RNA 测序
• GSE307545 主要组织相容性复合体 II 类 (MHC-II) 基因敲除小鼠在流感感染期间形成的记忆 B 细胞的转录谱分析。
• GSE284960 血红素对分化小鼠 B 细胞基因表达的影响 [RNA-seq]
• GSE319825 RNA测序研究探讨LITAF在调节暴露于缺氧/复氧环境的H9C2细胞基因表达谱中的作用
• GSE256465 新一代测序技术促进了经 ABA 或 UV-B 处理的 COL,uvr8 突变体转录组的定量分析
• GSE256188 超级增强子重组控制奥沙利铂耐药FBXW7突变型结直肠癌的再敏感性